The recently released ICH E14/S7B 2022 Q&As provides the best practice guidelines for evaluating the effect of preclinical compounds on the human ether-à-go-go-related gene (hERG) potassium channel1. The guidelines stipulate that in vitro hERG assessments should be performed to GLP compliance. In addition, it provides recommendations on the experimental methods that should be employed, the quality control parameters for analysing the data, as well as the preferred format for reporting the data. This is to ensure data quality, transparency and consistency throughout the industry. A hERG assay is considered negative if the safety margin calculated for the test article is greater than the established safety margins generated with the FDA’s positive controls (ondansetron, moxifloxacin and dofetilide) tested to the best practice guidelines. Metrion conducted a GLP compliant study using the conventional manual patch-clamp technique in accordance with the ICH E14/S7B Q&A best practice guidelines to establish in-house IC50 values for ondansetron, moxifloxacin and dofetilide.
Optical voltage imaging of human iPSC-derived cardiomyocytes was used to assess electrophysiological effects of compounds beyond hERG inhibition. Action potential waveform analysis revealed compound-specific and concentration-dependent changes, enabling mechanistic differentiation of multichannel activity and demonstrating a human-relevant approach for translational cardiac safety assessment.
The presence of sensory neuron markers, excitability properties consistent with sensory neurons, and evidence of nociceptor ion channels (using both RNASeq and electrophysiology) provides strong evidence that iCell Sensory Neurons have a robust sensory neuron phenotype suitable for supporting pain discovery programs.